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Omics studies in Behçet's disease. 贝赫切特氏病的 Omics 研究。
IF 5.2 2区 医学 Q1 RHEUMATOLOGY Pub Date : 2024-11-08 DOI: 10.1097/BOR.0000000000001067
Yesim Ozguler, Johannes Nowatzky

Purpose of review: In this review, we aimed to highlight recent findings from "-omics" studies in Behçet's disease.

Recent findings: Recent genomic studies in Behçet's disease identified possible risk loci associated with Behçet's disease related uveitis, neurologic involvement and gastrointestinal involvement. Additionally, sex-specific genetic effects were determined in Behçet's disease. Transcriptomic analyses of immune cells in Behçet's disease revealed that key inflammatory pathways such as NF-κB and MAPK have roles in Behçet's disease pathogenesis. Proteomic studies have highlighted the role of immune cell derived extracellular vesicles and identified potential biomarkers for vascular involvement and examined HLA I-bound immunopeptidomes. Metabolomics studies are still limited, but recent research has pointed to alterations in fatty acid metabolism and lipid profiles in Behçet's disease patient.

Summary: Omics studies have gained importance in the field of Behçet's disease through the generation of large data sets and efforts to extend their application are intensifying. These studies can provide opportunities for understanding Behçet's disease pathogenesis when they lead to testable hypotheses. Current challenges include the choice of appropriately homogeneous patient and control groups, effective data management and sharing, high cost and a rapidly increasing gap between the wealth of observational data generated and the relative paucity of controlled experimental efforts that could lead to mechanistic understanding.

综述的目的:在这篇综述中,我们旨在重点介绍贝赫切特病"-组学 "研究的最新发现:贝赫切特病的最新基因组研究发现了可能与贝赫切特病相关的葡萄膜炎、神经系统受累和胃肠道受累有关的风险位点。此外,还确定了贝赫切特病的性别特异性遗传效应。贝赫切特病免疫细胞的转录组分析表明,NF-κB 和 MAPK 等关键炎症通路在贝赫切特病发病机制中发挥作用。蛋白质组学研究强调了免疫细胞衍生的细胞外囊泡的作用,确定了血管受累的潜在生物标志物,并检查了与 HLA I 结合的免疫肽组。代谢组学研究仍然有限,但最近的研究表明,贝赫切特病患者的脂肪酸代谢和脂质谱发生了改变。摘要:通过生成大量数据集,Omics 研究在贝赫切特病领域变得越来越重要,扩大其应用范围的努力也在不断加强。这些研究如果能提出可检验的假设,就能为了解贝赫切特病的发病机制提供机会。目前面临的挑战包括:选择适当同质的患者组和对照组、有效的数据管理和共享、高昂的成本,以及所产生的大量观察性数据与可导致机理理解的对照实验工作相对匮乏之间迅速扩大的差距。
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引用次数: 0
Recent advances in immunometabolism in rheumatic diseases. 风湿病免疫代谢的最新进展。
IF 5.2 2区 医学 Q1 RHEUMATOLOGY Pub Date : 2024-11-08 DOI: 10.1097/BOR.0000000000001071
Ryo Hisada, Michihito Kono

Purpose of review: Aberrant autoreactive innate and adaptive immune responses cause systemic autoimmune diseases. Autoimmunity has been linked to abnormal metabolic states, and immunometabolism has emerged as a critical field in understanding the pathogenesis of rheumatic diseases. We aimed to explore the latest research on metabolic reprogramming in various immune cell types, including T cells, B cells, neutrophils, dendritic cells, monocytes, and macrophages, in the context of rheumatic diseases.

Recent findings: Each immune cell utilizes preferred metabolic pathways, and the cell activation dramatically modifies metabolic status. The inhibition of these pathways alters cell survival, differentiation, proliferation, and cytokine production - all of which contribute to rheumatic disease progression.

Summary: Targeting metabolic pathways or introducing anti-inflammatory metabolites, such as itaconate, could be novel therapeutic strategies for rheumatic diseases. Further research should focus on strategies for translating basic research findings to bedside applications.

综述的目的:异常的自身反应性先天性和适应性免疫反应会导致全身性自身免疫性疾病。自身免疫与异常代谢状态有关,免疫代谢已成为了解风湿性疾病发病机制的一个重要领域。我们旨在探索风湿病背景下各种免疫细胞类型(包括 T 细胞、B 细胞、中性粒细胞、树突状细胞、单核细胞和巨噬细胞)代谢重编程的最新研究成果:每种免疫细胞都利用首选的代谢途径,细胞活化会显著改变代谢状态。这些途径的抑制改变了细胞的存活、分化、增殖和细胞因子的产生--所有这些都会导致风湿性疾病的发展。总结:针对代谢途径或引入抗炎代谢物(如伊他康酸)可能是治疗风湿性疾病的新策略。进一步的研究应侧重于将基础研究成果转化为临床应用的策略。
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引用次数: 0
Systemic sclerosis: beyond skin and lung involvement. 系统性硬化症:不局限于皮肤和肺部受累。
IF 5.2 2区 医学 Q1 RHEUMATOLOGY Pub Date : 2024-11-01 Epub Date: 2024-10-03 DOI: 10.1097/BOR.0000000000001053
Monique Hinchcliff
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引用次数: 0
Understanding the gastrointestinal microbiome in systemic sclerosis: methodological advancements and emerging research. 了解系统性硬化症中的胃肠道微生物组:方法学进展和新兴研究。
IF 5.2 2区 医学 Q1 RHEUMATOLOGY Pub Date : 2024-11-01 Epub Date: 2024-08-23 DOI: 10.1097/BOR.0000000000001048
Alana J Haussmann, Zsuzsanna H McMahan, Elizabeth R Volkmann

Purpose of review: This review highlights the role of the gastrointestinal (GI) microbiome in systemic sclerosis (SSc). We describe techniques for evaluating the GI microbiome in humans, and emerging research linking GI microbiome alterations (i.e., dysbiosis) and distinct SSc clinical manifestations. We also address the evolving treatment landscape targeting dysbiosis in SSc.

Recent findings: Recent literature brings into focus the complex relationship between the GI microbiome and SSc pathogenesis. Advanced techniques (e.g., shotgun metagenomics, meta-transcriptomics) provide deeper insights into microbial taxonomy and active gene expression, exposing dysbiosis as a potential driver of SSc. New studies demonstrate that SSc patients who possess specific SSc clinical features, (e.g., interstitial lung disease), have unique GI microbiome profiles.

Summary: Dysbiosis is associated with specific clinical features in patients with SSc. New tools for studying the GI microbiome have furthered our understanding of the relationship between dysbiosis and SSc complications. Therapeutic avenues such as dietary adjustments, probiotics, antibiotics, mindfulness practices, and fecal transplants offer potential for managing SSc and preventing its progression through GI microbiome modulation. By clarifying what is known about the relationship between the GI dysbiosis, GI dysfunction, and SSc, this review enhances our understanding of SSc pathogenesis and proposes targeted interventions.

综述的目的:本综述强调了胃肠道微生物组在系统性硬化症(SSc)中的作用。我们介绍了评估人体胃肠道微生物组的技术,以及将胃肠道微生物组改变(即菌群失调)与不同的系统性硬化症临床表现联系起来的新兴研究。我们还讨论了针对 SSc 中菌群失调的不断发展的治疗方法:最近的文献聚焦于消化道微生物组与 SSc 发病机制之间的复杂关系。先进的技术(如霰粒元基因组学、元转录组学)使人们对微生物分类和活性基因表达有了更深入的了解,暴露出菌群失调是导致 SSc 的潜在因素。新研究表明,具有特定 SSc 临床特征(如间质性肺病)的 SSc 患者具有独特的消化道微生物组特征。研究消化道微生物组的新工具进一步加深了我们对菌群失调与 SSc 并发症之间关系的理解。饮食调整、益生菌、抗生素、正念练习和粪便移植等治疗途径为通过调节消化道微生物组来控制 SSc 和防止其恶化提供了可能。本综述通过阐明消化道菌群失调、消化道功能障碍和 SSc 之间的关系,加深了我们对 SSc 发病机制的了解,并提出了有针对性的干预措施。
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引用次数: 0
Interstitial lung disease and myositis. 间质性肺病和肌炎
IF 5.2 2区 医学 Q1 RHEUMATOLOGY Pub Date : 2024-11-01 Epub Date: 2024-08-12 DOI: 10.1097/BOR.0000000000001037
Takahisa Gono, Masataka Kuwana

Purpose of review: In patients with myositis, interstitial lung disease (ILD) is one of the major causes of morbidity and mortality. Given the limited evidence, there is an urgent need to refine the treatment for myositis-ILD. This review aims to highlight recent updates on the management of myositis-associated ILD, focusing on screening, risk stratification, and treatment.

Recent findings: Asian race and/or residence, dermatomyositis, mechanic's hand, antisynthetase antibodies, and antimelanoma differentiation-associated gene 5 antibodies are risk factors for ILD development. Patients with such risk factors should be screened for ILD using high-resolution computed tomography. Various prediction models for mortality or rapidly progressive ILD (RP-ILD) in patients with myositis-ILD have been proposed, but validation of these models in multiple independent studies is required. Academic societies in Japan, the United Kingdom, and the United States have proposed tentative treatment algorithms for myositis-ILD on the basis of the presence or absence of RP-ILD.

Summary: Knowledge on myositis-ILD risk stratification, potentially useful for personalized management approaches in clinical practice, is accumulating. However, further global joint efforts are necessary to build a strong evidence base for consensus algorithms for myositis-ILD.

审查目的:肌炎患者的间质性肺病(ILD)是发病和死亡的主要原因之一。由于证据有限,因此迫切需要完善肌炎间质性肺病的治疗方法。本综述旨在重点介绍肌炎相关ILD管理的最新进展,重点关注筛查、风险分层和治疗:亚洲人种和/或居住地、皮肌炎、机械手、抗异烟酸酶抗体和抗黑色素瘤分化相关基因5抗体是ILD发病的危险因素。应使用高分辨率计算机断层扫描对具有这些危险因素的患者进行 ILD 筛查。目前已提出了多种肌炎-ILD 患者死亡率或快速进展性 ILD(RP-ILD)的预测模型,但这些模型需要在多项独立研究中进行验证。日本、英国和美国的学术团体已根据是否存在 RP-ILD 提出了肌炎-ILD 的初步治疗算法。摘要:有关肌炎-ILD 风险分层的知识正在不断积累,这些知识可能有助于临床实践中的个性化管理方法。然而,要为肌炎-ILD 的共识算法奠定坚实的证据基础,还需要全球共同努力。
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引用次数: 0
Cross-tissue organization of myeloid cells in scleroderma and related fibrotic diseases. 硬皮病及相关纤维化疾病中髓细胞的跨组织结构。
IF 5.2 2区 医学 Q1 RHEUMATOLOGY Pub Date : 2024-11-01 Epub Date: 2024-09-11 DOI: 10.1097/BOR.0000000000001047
Ian D Odell

Purpose of review: Scleroderma and other fibrotic diseases have been investigated using single-cell RNA sequencing (scRNA-Seq), which has demonstrated enrichment in myeloid cell populations in multiple tissues. However, scRNA-Seq studies are inconsistent in their nomenclature of myeloid cell types, including dendritic cells, monocytes, and macrophages. Using cell type-defining gene signatures, I propose a unified nomenclature through analysis of myeloid cell enrichment across fibrotic tissues.

Recent findings: scRNA-Seq of human blood and skin identified a new subset of dendritic cells called DC3. DC3 express similar inflammatory genes to monocytes, including FCN1 , IL1B, VCAN, S100A8, S100A9 , and S100A12 . DC3 can be distinguished from monocytes by expression of EREG and Fc receptor genes such as FCER1A and FCGR2B . scRNA-Seq analyses of scleroderma skin and lung, idiopathic pulmonary fibrosis (IPF), COVID-19 lung fibrosis, myelofibrosis, and liver, kidney, and cardiac fibrosis all showed enrichment in myeloid cell types. Although they were called different names, studies of scleroderma skin and lung as well as liver cirrhosis datasets demonstrated enrichment in DC3. By contrast, lung, heart, and kidney fibrosis were enriched in SPP1 macrophages. High numbers of DC3 in the skin was associated with worse SSc skin and lung fibrosis severity.

Summary: scRNA-Seq of multiple diseases showed enrichment of DC3 in fibrotic skin, lung, and liver, whereas SPP1 macrophages occurred in fibrotic lung, heart, and kidney. Because DC3 and SPP1 macrophages showed organ-specific enrichment, understanding their signaling mechanisms across tissues will be important for future investigation.

综述目的:硬皮病和其他纤维化疾病的研究采用了单细胞 RNA 测序(scRNA-Seq)技术,该技术证明了多种组织中髓系细胞群的富集。然而,scRNA-Seq 研究对髓系细胞类型(包括树突状细胞、单核细胞和巨噬细胞)的命名并不一致。通过分析纤维化组织中髓系细胞的富集情况,我利用细胞类型定义基因特征,提出了一种统一的命名方法。最近的研究发现:人体血液和皮肤的 scRNA-Seq 发现了一种新的树突状细胞亚群,称为 DC3。DC3表达与单核细胞类似的炎症基因,包括FCN1、IL1B、VCAN、S100A8、S100A9和S100A12。对硬皮病皮肤和肺部、特发性肺纤维化(IPF)、COVID-19 肺纤维化、骨髓纤维化以及肝脏、肾脏和心脏纤维化进行的 scRNA-Seq 分析均显示髓系细胞类型富集。对硬皮病皮肤和肺部以及肝硬化数据集的研究虽然名称不同,但都显示了 DC3 的富集。相比之下,肺、心脏和肾脏纤维化则富含 SPP1 巨噬细胞。小结:多种疾病的 scRNA-Seq 数据集显示,纤维化的皮肤、肺部和肝脏富含 DC3,而纤维化的肺部、心脏和肾脏则富含 SPP1 巨噬细胞。由于 DC3 和 SPP1 巨噬细胞表现出器官特异性富集,因此了解它们在不同组织中的信号转导机制对未来的研究非常重要。
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引用次数: 0
From traditional to targeted: the changing trajectory of therapies in dermatomyositis. 从传统疗法到靶向疗法:皮肌炎疗法的变化轨迹。
IF 5.2 2区 医学 Q1 RHEUMATOLOGY Pub Date : 2024-11-01 Epub Date: 2024-08-13 DOI: 10.1097/BOR.0000000000001041
Rochelle L Castillo, Kimberly Hashemi, Elizabeth Rainone, Katharina S Shaw, Ruth Ann Vleugels

Purpose of review: New breakthroughs in our understanding of dermatomyositis (DM) have spawned the recent development of novel agents that specifically target key drivers in DM immunopathogenesis. This review aims to provide a comprehensive overview of new and forthcoming therapies for DM and to highlight their mechanisms of action, best evidence to date, and potential impact on disease management.

Recent findings: Strategies that either counteract dysregulated interferon signaling [via the inhibition of interferon β, the type I interferon receptor subunit 1 (IFNAR1), or janus kinase (JAK)-signal transducer and activator of transcription (STAT) transduction] or induce durable autoreactive B cell depletion through chimeric antigen receptor (CAR) T-cell therapy appear to hold the most promise for sustained remission in DM.

Summary: The trajectory of DM treatments is rapidly evolving, fueled by the unparalleled insights provided by multiomic studies and big data analysis pipelines. Targeted therapies that maximize both efficacy and safety have the potential to complement or replace traditional immunosuppressives and revolutionize the approach to the management of DM.

综述的目的:我们对皮肌炎(Dermatomyositis,DM)的认识有了新的突破,因此最近开发出了专门针对DM免疫发病机制关键驱动因素的新型药物。本综述旨在全面概述皮肌炎的新疗法和即将推出的疗法,并重点介绍其作用机制、迄今为止的最佳证据以及对疾病管理的潜在影响:最近的发现:通过抑制干扰素β、I型干扰素受体亚基1(IFNAR1)或破伤风激酶(JAK)-信号转导和转录激活因子(STAT)转导来对抗失调的干扰素信号转导,或通过嵌合抗原受体(CAR)T细胞疗法诱导持久的自反应性B细胞耗竭,这些策略似乎最有希望实现DM的持续缓解。摘要:在多组学研究和大数据分析管道提供的无与伦比的洞察力的推动下,DM 的治疗轨迹正在迅速发展。最大限度提高疗效和安全性的靶向疗法有可能补充或取代传统的免疫抑制剂,并彻底改变 DM 的治疗方法。
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引用次数: 0
Editorial myositis and myopathies. 编辑肌炎和肌病。
IF 5.2 2区 医学 Q1 RHEUMATOLOGY Pub Date : 2024-11-01 Epub Date: 2024-10-03 DOI: 10.1097/BOR.0000000000001056
David Fiorentino, Livia Casciola-Rosen
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引用次数: 0
Editorial introductions. 编辑介绍。
IF 5.2 2区 医学 Q1 RHEUMATOLOGY Pub Date : 2024-11-01 Epub Date: 2024-10-03 DOI: 10.1097/BOR.0000000000001046
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引用次数: 0
Gastrointestinal disease in systemic sclerosis: the neglected organ system? 系统性硬化症的胃肠道疾病:被忽视的器官系统?
IF 5.2 2区 医学 Q1 RHEUMATOLOGY Pub Date : 2024-11-01 Epub Date: 2024-08-28 DOI: 10.1097/BOR.0000000000001052
Zsuzsanna McMahan, John Pandolfino, Harris Perlman, Francesco Del Galdo, Monique Hinchcliff

Purpose of review: Identifying outcomes and clinical trial endpoints enabled the discovery of new inflammatory bowel disease (IBD) treatments. Herein, we describe efforts to advance the study of gastrointestinal (GI) manifestations in systemic sclerosis (SSc).

Recent findings: Insights into the scope of the problem, as well as advancements in the measurement and treatment of SSc-GI, are underway. Proposed SSc esophageal endophenotypes are now defined, risk stratification methods are growing, and imaging and functional studies are now employed to guide therapeutic interventions. Additional progress is being made in characterizing the gut microbiome in patients with SSc. Research into the role of the immune response in the pathogenesis of SSc-GI disease is also ongoing, evolving simultaneously with the development of methods to facilitate data collection with real-time capture of diet, exercise, and medication data.

Summary: Multidisciplinary teams are working to deepen our understanding of SSc-GI disease pathogenesis, to identify biomarkers for risk stratification and the assessment of disease activity, and to develop and validate outcomes and clinical trial endpoints to pave the way toward effective therapy for SSc-GI disease.

综述目的:确定结果和临床试验终点有助于发现新的炎症性肠病(IBD)治疗方法。在此,我们将介绍为推动系统性硬化症(SSc)胃肠道(GI)表现的研究而做出的努力:最近的发现:我们正在深入了解这一问题的范围,并在 SSc-GI 的测量和治疗方面取得进展。目前已确定了拟议的 SSc 食管内型,风险分层方法也在不断发展,成像和功能研究已被用于指导治疗干预。在确定 SSc 患者肠道微生物组的特征方面也取得了进展。对免疫反应在 SSc-GI 疾病发病机制中的作用的研究也在进行中,与此同时,通过实时采集饮食、运动和用药数据来促进数据收集的方法也在不断发展。总结:多学科团队正在努力加深我们对 SSc-GI 疾病发病机制的了解,确定用于风险分层和疾病活动评估的生物标志物,并开发和验证结果和临床试验终点,为 SSc-GI 疾病的有效治疗铺平道路。
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引用次数: 0
期刊
Current opinion in rheumatology
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